Systematically uncovering the absorbed effective substances of Radix
scutellaria-licorice drug pair in rat plasma against COVID-19 using a
combined UHPLC-Q-TOF-MS analysis and target network pharmacology
Abstract
Rationale: Radix scutellaria-Licorice drug pair (RSLDP), a frequently
used herbal pair with the effect of clearing heat and detoxifying, is
the commonly employed drug pair in TCM prescription for the treatment of
COVID-19. Until now, the metabolism feature and anti-COVID-19 mechanism
of RSLDP have not been fully elucidated. Methodology: In this study, a
sensitive and rapid method was developed for the separation and
identification of the absorbed constituents of RSLDP in the rat plasma
by UHPLC-QTOF-MS. Besides, we optimized the conventional process ways of
network pharmacology and proposed a new concept called target network
pharmacology (T-NP). It used the absorbed constituents and the
corresponding targets to generate compound-target network, and compare
to the conventional network pharmacology, it could reduce the false
positive results. Results: A total of 85 absorbed constituents were
identified or tentatively characterized in dosed plasma,including 32
components in Radix Scutellaria,27 components in Licorice and 65
components in RSLDP. The results showed that the compatibility of Radix
Scutellaria and Licorice increased the quantity of components in vivo.
We found that 106 potential targets of 64 active compounds in RSLDP were
related to COVID-19.And 12 targets (MAPK3,IL6,JUN,IL2,STAT3,
AKT1,TNF,STAT1,EGFR,HSP9AA1,VEGFA,RELA) could be core targets for RSLDP
in treating COVID-19. Conclusions: The metabolism feature of RSLDP in
vivo was systematically uncovered. The combining use of the T-NP method
could discover potential drug targets and disclose the biological
processes of RSLDP, which will clarify the potential mechanisms of RSLDP
in the treatment of COVID-19.